Immunologic and metabolic features of pancreatic ductal adenocarcinoma define prognostic subtypes of disease

Clinical Cancer Research

Volumn 22, Issue 14, 2016, Pages 3606-3617

  Hutcheson, Jack ^a   Balaji, Uthra ^a   Porembka, Matthew R ^b,c   Wachsmann, Megan B ^c   McCue, Peter A ^d   Knudsen, Erik S ^a,b   Witkiewicz, Agnieszka K ^a,b,c  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^d THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD163 ANTIGEN; MONOCARBOXYLATE TRANSPORTER 4; PROGRAMMED DEATH 1 LIGAND 1; TRANSCRIPTION FACTOR FOXP3; BIOLOGICAL MARKER; CELL SURFACE RECEPTOR; DIFFERENTIATION ANTIGEN; FORKHEAD TRANSCRIPTION FACTOR; LEUKOCYTE ANTIGEN;

ADULT; AGED; ARTICLE; BONE MARROW CELL; CANCER PATIENT; CANCER PROGNOSIS; CANCER SIZE; CANCER STAGING; CANCER SURVIVAL; CELL DIFFERENTIATION; CELL TRANSFORMATION; CONTROLLED STUDY; FEMALE; GLYCOLYSIS; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; LYMPH NODE METASTASIS; MACROPHAGE FUNCTION; MAJOR CLINICAL STUDY; MALE; PANCREAS ADENOCARCINOMA; PANCREATIC CANCER CELL LINE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TISSUE MICROARRAY; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; ADENOCARCINOMA; IMMUNOLOGY; METABOLISM; MIDDLE AGED; PANCREAS CARCINOMA; PANCREAS TUMOR; PROGNOSIS; TUMOR CELL LINE; VERY ELDERLY;

ADENOCARCINOMA; ADULT; AGED; AGED, 80 AND OVER; ANTIGENS, CD; ANTIGENS, DIFFERENTIATION, MYELOMONOCYTIC; B7-H1 ANTIGEN; BIOMARKERS; CARCINOMA, PANCREATIC DUCTAL; CELL LINE, TUMOR; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; MALE; MIDDLE AGED; PANCREATIC NEOPLASMS; PROGNOSIS; RECEPTORS, CELL SURFACE; TUMOR MICROENVIRONMENT;

EID: 84978516901     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-15-1883     Document Type: Article

References (49)

1. Fokas E, O'neill E, Gordon-Weeks A, Mukherjee S, Mckenna WG, Muschel RJ. Pancreatic ductal adenocarcinoma: from genetics to biology to radiobiology to oncoimmunology and all the way back to the clinic. Biochim Biophys Acta 2014;1855:61-82.
2. Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg 2004;91:586-94.
3. Franco J, Witkiewicz AK, Knudsen ES. CDK4/6 inhibitors have potent activity in combination with pathway selective therapeutic agents in models of pancreatic cancer. Oncotarget 2014;5:6512-25.
4. Baek G, Tse YF, Hu Z, Cox D, Buboltz N, Mccue P, et al. MCT4 defines a glycolytic subtype of pancreatic cancer with poor prognosis and unique metabolic dependencies. Cell Rep 2014;9:2233-49.
5. Ino Y, Yamazaki-Itoh R, Shimada K, Iwasaki M, Kosuge T, Kanai Y, et al. Immune cell infiltrationasan indicator oftheimmunemicroenvironment of pancreatic cancer. Br J Cancer 2013;108:914-23.
6. Jamieson NB, Mohamed M, Oien KA, Foulis AK, Dickson EJ, Imrie CW, et al. The relationship between tumor inflammatory cell infiltrate and outcome in patients with pancreatic ductal adenocarcinoma. Ann Surg Oncol 2012;19:3581-90.
7. Tjomsland V, Niklasson L, Sandstrom P, Borch K, Druid H, Bratthall C, et al. The desmoplastic stroma plays an essential role in the accumulation and modulation of infiltrated immune cells in pancreatic adenocarcinoma. Clin Dev Immunol 2011;2011:212810.
8. Hartel M, Di Mola FF, Gardini A, Zimmermann A, Di Sebastiano P, Guweidhi A, et al. Desmoplastic reaction influences pancreatic cancer growth behavior. World J Surg 2004;28:818-25.
9. Kleeff J, Beckhove P, Esposito I, Herzig S, Huber PE, Lohr JM, et al. Pancreatic cancer microenvironment. Int J Cancer 2007;121:699-705.
10. Hiraoka N, Onozato K, Kosuge T, Hirohashi S. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res 2006;12: 5423-34.
11. Benson DD, Meng X, Fullerton DA, Moore EE, Lee JH, Ao L, et al. Activation state of stromal inflammatory cells in murine metastatic pancreatic adenocarcinoma. Am J Physiol Regul Integr Comp Physiol 2012;302: R1067-75.
12. Asari S, Matsumoto I, Toyama H, Shinzeki M, Goto T, Ishida J, et al. Preoperative independent prognostic factors in patients with borderline resectable pancreatic ductal adenocarcinoma following curative resection: the neutrophil-lymphocyte and platelet-lymphocyte ratios. Surg Today . 2015 Jun 25. [Epub ahead of print].
13. Gunderson AJ, Kaneda MM, Tsujikawa T, Nguyen AV, Affara NI, Ruffell B, et al. Bruton's Tyrosine Kinase (BTK)-dependent immune cell crosstalk drives pancreas cancer. Cancer Discov . 2015 Dec 29. [Epub ahead of print].
14. Xu YF, Lu Y, Cheng H, Shi S, Xu J, Long J, et al. Abnormal distribution of peripheral lymphocyte subsets induced by PDAC modulates overall survival. Pancreatology 2014;14:295-301.
15. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366:2455-65.
16. Tan Z, Xie N, Banerjee S, Cui H, Fu M, Thannickal VJ, et al. The monocarboxylate transporter 4 is required for glycolytic reprogramming and inflammatory response in macrophages. J Biol Chem 2015;290:46-55.
17. Wei L, Zhou Y, Yao J, Qiao C, Ni T, Guo R, et al. Lactate promotes PGE2 synthesis and gluconeogenesis in monocytes to benefit the growth of inflammation-associated colorectal tumor. Oncotarget 2015;6:16198-214.
18. Peter K, Rehli M, Singer K, Renner-Sattler K, Kreutz M. Lactic acid delays the inflammatory response of human monocytes. Biochem Biophys Res Commun 2015;457:412-8.
19. Lee KE, Spata M, Bayne LJ, Buza EL, Durham AC, Allman D, et al. Hif1alpha deletion reveals pro-neoplastic function of B cells in pancreatic neoplasia. Cancer Discov . 2015 Dec 29. [Epub ahead of print].
20. Miller BW, Morton JP, Pinese M, Saturno G, Jamieson NB, Mcghee E, et al. Targeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of Lox abrogates metastasis and enhances drug efficacy. EMBO Mol Med 2015;7:1063-76.
21. Witkiewicz AK, Whitaker-Menezes D, Dasgupta A, Philp NJ, Lin Z, Gandara R, et al. Using the Reverse Warburg Effect to identify high-risk breast cancer patients: stromal MCT4 predicts poor clinical outcome in triplenegative breast cancers. Cell Cycle 2012;11:1108-17.
22. Gallagher SM, Castorino JJ, Wang D, Philp NJ. Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line Mda-Mb-231. Cancer Res 2007;67:4182-9.
23. Nomi T, Sho M, Akahori T, Hamada K, Kubo A, Kanehiro H, et al. Clinical significance and therapeutic potential of the programmed death-1 ligand/ programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res 2007;13:2151-7.
24. Geng L, Huang D, Liu J, Qian Y, Deng J, Li D, et al. B7-H1 up-regulated expression in human pancreatic carcinoma tissue associates with tumor progression. J Cancer Res Clin Oncol 2008;134:1021-7.
25. R-Core-Team. R: A Language and environment for statistical computing . Vienna, Austria: R Foundation For Statistical Computing; 2014.
26. Shi T, Seligson D, Belldegrun AS, Palotie A, Horvath S. Tumor classification by tissue microarray profiling: random forest clustering applied to renal cell carcinoma. Mod Pathol 2005;18:547-57.
27. Hutcheson J, Perlman H. Loss of Bim results in abnormal accumulation of mature CD4-CD8-CD44-CD25- thymocytes. Immunobiology 2007;212: 629-36.
28. Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 2002;169:2756-61.
29. Linehan DC, GoedegebuurePS. CD25+ CD4+ regulatory T-cells in cancer. Immunol Res 2005;32:155-68.
30. Curiel TJ. Regulatory T cells and treatment of cancer. Curr Opin Immunol 2008;20:241-6.
31. Shieh JH, Cini JK, Wu MC, Yunis AA. Purification and characterization of human colony-stimulating factor 1 from human pancreatic carcinoma (MIA Paca-2) cells. Archiv Biochem Biophys 1987;253:205-13.
32. Ghesquiere B, Wong BW, Kuchnio A, Carmeliet P. Metabolism of stromal and immune cells in health and disease. Nature 2014;511:167-76.
33. Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, et al. Phase 2 trial of single agent ipilimumab (Anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 2010;33:828-33.
34. Le DT, Lutz E, Uram JN, Sugar EA, Onners B, Solt S, et al. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother 2013;36:382-9.
35. Zhu Y, Knolhoff BL, Meyer MA, Nywening TM, West BL, Luo J, et al. CSF1/ CSF1R blockade reprograms tumor-infiltrating macrophages andimproves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res 2014;74:5057-69.
36. Jiang Y, DuZ, Yang F, DiY, LiJ, ZhouZ, etal. FOXP3+ lymphocyte density in pancreatic cancer correlates with lymph node metastasis. PLos One 2014;9:E106741.
37. Yoshikawa K, Mitsunaga S, Kinoshita T, Konishi M, Takahashi S, Gotohda N, et al. Impact of tumor-associated macrophages on invasive ductal carcinoma of the pancreas head. Cancer Sci 2012;103:2012-20.
38. Bayne LJ, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ, et al. Tumorderived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 2012;21:822-35.
39. Pylayeva-Gupta Y, Lee KE, Hajdu CH, Miller G, Bar-Sagi D. Oncogenic Krasinduced GM-CSF production promotes the development of pancreatic neoplasia. Cancer Cell 2012;21:836-47.
40. Liou GY, Doppler H, Necela B, Edenfield B, Zhang L, Dawson DW, et al. Mutant KRAS-induced expression of ICAM-1 in pancreatic acinar cells causes attraction of macrophages to expedite the formation of precancerous lesions. Cancer Discov 2015;5:52-63.
41. Kodumudi KN, Woan K, Gilvary DL, Sahakian E, Wei S, Djeu JY. A novel chemoimmunomodulating property of docetaxel: suppression of myeloid-derived suppressor cells in tumor bearers. Clin Cancer Res 2010;16:4583-94.
42. Nagaraj S, Nelson A, Youn JI, Cheng P, Quiceno D, Gabrilovich DI. Antigen-specific CD4(+) T cells regulate function of myeloid-derived suppressor cells in cancer via retrograde MHC class II signaling. Cancer Res 2012;72:928-38.
43. Meng F, Li C, Li W, Gao Z, Guo K, Song S. Interaction between pancreatic cancer cells and tumor-associated macrophages promotes the invasion of pancreatic cancer cells and the differentiation and migration of macrophages. IUBMB Life 2014;66:835-46.
44. Liu CY, Xu JY, Shi XY, Huang W, Ruan TY, Xie P, et al. M2-polarized tumorassociated macrophages promoted epithelial-mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway. Lab Invest 2013;93:844-54.
45. Solinas G, Schiarea S, Liguori M, Fabbri M, Pesce S, Zammataro L, et al. Tumor-conditioned macrophages secrete migration-stimulating factor: a new marker for M2-polarization, influencing tumor cell motility. J Immunol 2010;185:642-52.
46. Weizman N, Krelin Y, Shabtay-Orbach A, Amit M, Binenbaum Y, Wong RJ, et al. Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase. Oncogene 2014;33: 3812-9.
47. Panni RZ, Sanford DE, Belt BA, Mitchem JB, Worley LA, Goetz BD, et al. Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer. Cancer Immunol Immunother 2014;63: 513-28.
48. Colegio OR, Chu NQ, Szabo AL, Chu T, Rhebergen AM, Jairam V, et al. Functional polarization of tumour-associated macrophages by tumourderived lactic acid. Nature 2014;513:559-63.
49. Daemen A, Peterson D, Sahu N, Mccord R, Du X, Liu B, et al. Metabolite profiling stratifies pancreatic ductal adenocarcinomas into subtypes with distinct sensitivities to metabolic inhibitors. Proc Natl Acad Sci U S A 2015;112:E4410-7.